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ABIRPRED

Cancer Type: Genitourinary, Prostate  Intent: Palliative
Regimen Category: Evidence-Informed
Funding:
Exceptional Access Program
    abiraterone - Metastatic castrate-resistant prostate cancer, with specific criteria
ODB - General Benefit
    prednisone
A - Regimen Name

ABIRPRED Regimen
Abiraterone-Prednisone


Disease Site
Genitourinary - Prostate

Intent
Palliative

Regimen Category
Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.


Rationale and Uses
  • For the treatment of metastatic, castrate-resistant prostate cancer (mCRPC) in combiation with ADT and prednisone, in patients who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy, have no history of viral hepatitis / chronic liver disease / significant cardiac disease and have not received prior chemotherapy (EAP criteria)
  • For the treatment of metastatic, castrate-resistant prostate cancer in combination with ADT and prednisone, in patients who have progressed after prior chemotherapy containing docetaxel
  • Abiraterone is not funded for combination treatment with cabazitaxel or enzalutamide, in patients who have received prior chemotherapy for mCRPC or in newly diagnosed hormone-sensitive high-risk metastatic prostate cancer

 


Supplementary Public Funding

abiraterone
Exceptional Access Program (abiraterone - Metastatic castrate-resistant prostate cancer, with specific criteria) (EAP Website)

prednisone
ODB - General Benefit (prednisone) (

ODB Formulary

)

 
B - Drug Regimen

abiraterone
1000 mg PO once daily

(Outpatient prescription in 250 mg and 500 mg tablets)

 

prednisone
1
10 mg PO once daily

(Outpatient prescription in 5 mg tablets)

 

Patients should continue to receive GnRH agonists during abiraterone treatment unless they have had prior orchiectomy.

1 The phase III trial in asymptomatic/ mildly symptomatic patients used prednisone 5mg PO BID.
 
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C - Cycle Frequency

CONTINUOUS TREATMENT

Until disease progression or unacceptable toxicity

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Minimal

Other Supportive Care:

  • May require increased corticosteroid dosage before, during and after periods of unusual stress such as surgery or trauma

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. Control hypertension and correct hypokalemia before treatment.

Dosage with toxicity

Toxicity
Action
Abiraterone dose
Prednisone dose

Grade 3 ALT/AST

OR

Grade 3 total bilirubin

Hold; monitor liver function closely until recovery to baseline THEN

Reduce to 500mg/day

No change

Grade 4 LFTs

OR

ALT/AST > 3 x ULN AND total bilirubin > 2 x ULN (in the absence of biliary obstruction or other causes)

OR ≥ Grade 3 ↑ LFTs after dose modification

OR myopathy/rhabdomyolysis

OR confirmed pneumonitis/allergic alveolitis

 

 

Discontinue permanently Not applicable Not applicable
Toxicity (continued) Action Abiraterone dose Prednisone dose
Hypokalemia persists despite optimal K supplements and adequate oral intake

Or

Other mineralcorticoid effects persist
  No change If on 5mg/day, may increase to 10 mg/day

 



Hepatic Impairment

Increased exposure and half-life have been observed in patients with hepatic impairment at baseline; abiraterone has not been studied in patients with moderate or severe hepatic impairment and should not be used. (Patients with moderate to severe hepatic impairment, active hepatitis, chronic liver disease or ascites were excluded from clinial trials.) 

Refer to the table above for dose modifications with hepatotoxicity during treatment.

No dose adjustment required for prednisone. 

 
Hepatic Impairment (at baseline) Dose
Mild (Child-Pugh Class A) No change
Moderate (Child-Pugh Class B) Do not use abiraterone
Severe (Child-Pugh Class C) Do not use abiraterone

Renal Impairment

No dose adjustment required for prednisone or abiraterone.


Dosage in the Elderly

No overall differences in effectiveness or adverse effects were seen between elderly and younger patients.


 
F - Adverse Effects

Refer to abiraterone, prednisone drug monograph(s) for additional details of adverse effects


Very common (≥ 50%)

Common (25-49%)

Less common (10-24%)

Uncommon (< 10%),

but may be severe or life-threatening

  • Increased triglycerides, cholesterol
  • Increased LFTs (may be severe)
  • Fatigue
  • Musculoskeletal pain
  • Edema
  • Abnormal electrolytes / mineralocorticoid effects
  • Constipation
  • Diarrhea
  • Androgen deprivation symptoms
  • Hypertension
  • Cough, dyspnea
  • Nausea, vomiting
  • Dyspepsia
  • Anemia
  • Urinary symptoms
  • Steroid effects (weight gain, hyperglycemia, insomnia, myopathy, cataracts,osteoporosis)
  • Arrhythmia
  • Arterial thromboembolism
  • Cardiotoxicity
  • Adrenal insufficiency
  • Pneumonitis/allergic alveolitis
  • Rhabdomyolysis
 
G - Interactions

Refer to abiraterone drug monograph(s) for additional details


  • Avoid co-administration with CYP2D6 substrates with narrow therapeutic range due to increased risk of toxicity. If must co-administer, consider dose reduction of 2D6 substrate.
  • Avoid strong CYP3A4 inducers due to risk of reduced efficacy.
  • Avoid strong CYP3A4 inhibitors due to increased risk of toxicity.
  • Avoid spironolactone as this may stimulate disease progression.
  • Caution when co-administered with drugs that increase risk of myopathy/rhabdomyolysis
 
H - Drug Administration and Special Precautions

Refer to abiraterone, prednisone drug monograph(s) for additional details


Administration:

  • Abiraterone must be taken on an empty stomach.  No solid or liquid food should be eaten for at least 2 hours before and at least 1 hour after the dose.
  • The tablets should be swallowed whole with a glass of water.
  • If an abiraterone dose is missed, skip this and take the next dose as scheduled. Do not double the dose to make up for the missed one.
  • Since abiraterone may harm the fetus, women who are pregnant or who may become pregnant should handle abiraterone with protection (e.g. gloves).

 

Contraindications:

  • Women who are or may potentially be pregnant (not for use in women)
  • Patients who have a hypersensitivity to this drug or any of its components
  • Moderate-severe hepatic impairment at baseline
  • Severe (grade 4) hepatotoxicity

 

Warnings/precautions:

 

  • Use with caution in patients with cardiovascular disease as they were not included in clinical trials. Increased mineralocorticoid levels from CYP17 inhibition may cause hypertension, hypokalemia and fluid retention. Use with caution in patients whose underlying medical conditions may be affected by these effects.
  • Use with caution in patients taking other medications associated with myopathy or rhabdomyolysis (e.g. statins)
  • Adrenal insufficiency has been reported in patients taking abiraterone and prednisone. Increased corticosteroid dosage may be required before, during and after the stressful situation.
  • Contains lactose and should not be used in patients with hereditary galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.
  • Efficacy may be lower in patients who have been treated previously with ketoconazole for their prostate cancer.
  • The safety and efficacy of combination abiraterone and cytotoxic chemotherapy use has not been established.

 

 

 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Recommended Clinical Monitoring

  • Blood pressure, serum potassium; baseline and monthly
  • Cholesterol and triglycerides; baseline, every 2 to 3 months and as clinically indicated.
  • Liver function tests, bilirubin; baseline, every 2 weeks for the first 3 months and monthly thereafter, or as clinically indicated
  • Monitor for adrenal insufficiency; as clinically indicated when prednisone is withdrawn, or during periods of infection/stress
  • Monitor for mineralocorticoid excess; as clinically indicated if patient continues on abiraterone after stopping prednisone
  • Clinical toxicity assessment for hypertension, edema, GI, musculoskeletal or steroid side effects, hot flashes, urinary symptoms, cardiac and respiratory toxicity; at each visit
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


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J - Administrative Information

Outpatient prescription for home administration


 
K - References

Abiraterone drug monograph, Cancer Care Ontario.

de Bono JS., Logothetis CJ, Molina A, et al.  Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011;364:1995-2005.

Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 2013;368(2):138-48.


July 2018 Updated rationale and use, dose modifications, adverse effects, contraindications sections


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M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.